1. Field of Invention
The present invention is directed to photoluminescent semiconductor nanocrystals and a method for enhanced biological imaging and analyte detection using near-infrared emissions.
2. Brief Description of the Prior Art
Semiconductor nanocrystals, hereinafter referred to as quantum dots (QDs), with surface bioconjugates have been studied extensively because of their unique optical properties. QDs are inorganic nanoparticles that emit light at a specific wavelength when excited. When light impinges on the QDs, electrons in the valence band are excited to the conduction band, forming short-lived (nanoseconds) electron-hole pairs called excitons that emit photons of a specific wavelength when the electron-hole pairs eventually recombine. The excitonic emission is not as dependent on the excitation light wavelength as that of fluorescent molecules. Therefore it is easier to excite QDs to luminescence than to excite traditional fluorescent molecules that require a specific excitation wavelength. The wavelength of the emitted photons of QDs, however, is specific to and controlled by the composition of the QDs and defect states inside the energy gap.
In the last few years, the interest in using QDs in biomedical imaging has exploded due to advances in surface modification of QDs that have made them accessible for antibody immobilization and detection of antibody-antigen binding. QDs may be used as imaging markers inside living organisms and may also be used as biological markers to find a disease as well as to carry a drug to the exact cell that needs it by immobilizing antibodies on the surface of the QDs. QDs may be specific to a particular disease and may be tailored to bind only to infected cells. Detection may be carried out either by locating the QDs' particles or by detecting signals emanating from the QDs' particles. For example, luminescence of antibody-coated QDs bound to the cancerous tissue in a mouse helped to locate a tumor (Quantum Dots Get Wet, Science, volume 300, p. 80, Apr. 4, 2003). Until now the main biological tags that have been employed are organic fluorophores or radioactive labels (S. G. Penn, L. He, and M. J. Natan, “Nanoparticles for Bioanalysis”, Curr. Opin. Chem. Bio., 7, 1-7, (2003)). Radioactive labels are short lived and radioactive. Concerns about the use of radioactive materials in the body always arise. Organic fluorophores have wide emission spectra and the emission is not as bright as that of QDs. In comparison to conventional dye molecules, QDs have the advantages of having tunable fluorescence signatures, narrow emission spectra, brighter emissions, and good photostability (M. L. Brongersma, “Nanoshells, “Gifts in a Gold Wrapper”, Nature Materials, vol. 2, May 2003). The fabrication process of water-soluble luminescent QDs, however, is prohibitively expensive and complex, typically requiring the elimination of QD broadband emissions, thus compromising the commercializability of the QDs.
Recently, there has been a significant amount of interest in developing effective near infrared (NIR) emission QDs that enable deep tissue imaging, such as is addressed, for example, in U.S. Patent Publication No. 20080039816. Notably, these quantum dots may be fabricated from a wide variety of materials including CdS. Other references such as U.S. Patent Publication 2008/0057311 also disclose QDs fabricated from nanocrystalline materials, such as CdS and PbS. These references, however, do not appear to disclose a lead cadmium compound QD, such as Cd1-xPbxS, that is capable of NIR emission. Thus, there remains a need to develop highly luminescent QDs capable of producing a near-infrared emission without expressing undesirable broadband emissions.